BACKGROUND:Some studies have confirmed the changes in the function of immune cell subsets such as monocytes,T cells,B cells,and natural killer cells(NK cells)in patients with osteoarthritis,but the specific regulatory mechanisms are unclear.OBJECTIVE:To explore the causal relationship between plasma metabolite-mediated immune cells and hip osteoarthritis.METHODS:The Genome-Wide Association Studies(GWAS)data of 731 immune cells were used as the exposure,the GWAS data of hip osteoarthritis were used as the outcome,and 1 400 plasma metabolites were selected as mediating factors.The GWAS database is an important database for genetic association studies,maintained by international organizations with no country-specific affiliation.The inverse variance weighting method in the two-sample Mendelian randomization method was the main method,and the Bayesian weighted Mendelian randomization method was used to analyze the prior distribution,sample data and weights,which were then used to calculate the posterior distribution.The accuracy and reliability of the inverse variance weighting results were evaluated according to the posterior distribution,supplemented by MR-Egger,weighted median,simple model,and weighted mode methods.The pliotropy test and heterogeneity test were used to ensure the robustness of the process.The results of the inverse variance weighting method were used for subsequent mediating effect analysis.RESULTS AND CONCLUSION:(1)The inverse variance weighting method identified 4 immune cells strongly correlated with hip osteoarthritis,and 20 metabolites strongly associated with hip osteoarthritis,all of which had no reverse causal relationship.At the same time,the validation results of Bayesian weighted Mendelian randomization method showed that the posterior mean value was similar to the estimated value of the inverse variance weighting,and the posterior variance was relatively lower.One monocyte subtype(PDL-1 on CD14-CD16+)was finally screened out to have a causal relationship with hip osteoarthritis,with a total effect of-0.047(odds ratio=0.954,95％confidence interval:0.926-0.983),and a mediating effect of-0.004(odds ratio=0.939,95％confidence interval:0.902-0.978)mediated by alliin levels,accounting for 8.5％of the total effect.It was concluded that alliin is a protective factor in the progression of hip osteoarthritis,in which this metabolite plays a mediating role.(2)The large amount of data from international databases and European population analysis is of great significance to Chinese biomedicine,which can provide clues for research on the genetic susceptibility to similar diseases in the Chinese population,aiding in discovering the unique associations.The pharmacogenomic approaches used can be adapted to screen for drug response genes in the Chinese population,enhancing the precision of personalized medicine.Additionally,the advanced high-throughput technologies and statistical methods employed can be learned and applied to disease prevention and treatment research.

BACKGROUND:Some studies have confirmed the changes in the function of immune cell subsets such as monocytes,T cells,B cells,and natural killer cells(NK cells)in patients with osteoarthritis,but the specific regulatory mechanisms are unclear.OBJECTIVE:To explore the causal relationship between plasma metabolite-mediated immune cells and hip osteoarthritis.METHODS:The Genome-Wide Association Studies(GWAS)data of 731 immune cells were used as the exposure,the GWAS data of hip osteoarthritis were used as the outcome,and 1 400 plasma metabolites were selected as mediating factors.The GWAS database is an important database for genetic association studies,maintained by international organizations with no country-specific affiliation.The inverse variance weighting method in the two-sample Mendelian randomization method was the main method,and the Bayesian weighted Mendelian randomization method was used to analyze the prior distribution,sample data and weights,which were then used to calculate the posterior distribution.The accuracy and reliability of the inverse variance weighting results were evaluated according to the posterior distribution,supplemented by MR-Egger,weighted median,simple model,and weighted mode methods.The pliotropy test and heterogeneity test were used to ensure the robustness of the process.The results of the inverse variance weighting method were used for subsequent mediating effect analysis.RESULTS AND CONCLUSION:(1)The inverse variance weighting method identified 4 immune cells strongly correlated with hip osteoarthritis,and 20 metabolites strongly associated with hip osteoarthritis,all of which had no reverse causal relationship.At the same time,the validation results of Bayesian weighted Mendelian randomization method showed that the posterior mean value was similar to the estimated value of the inverse variance weighting,and the posterior variance was relatively lower.One monocyte subtype(PDL-1 on CD14-CD16+)was finally screened out to have a causal relationship with hip osteoarthritis,with a total effect of-0.047(odds ratio=0.954,95％confidence interval:0.926-0.983),and a mediating effect of-0.004(odds ratio=0.939,95％confidence interval:0.902-0.978)mediated by alliin levels,accounting for 8.5％of the total effect.It was concluded that alliin is a protective factor in the progression of hip osteoarthritis,in which this metabolite plays a mediating role.(2)The large amount of data from international databases and European population analysis is of great significance to Chinese biomedicine,which can provide clues for research on the genetic susceptibility to similar diseases in the Chinese population,aiding in discovering the unique associations.The pharmacogenomic approaches used can be adapted to screen for drug response genes in the Chinese population,enhancing the precision of personalized medicine.Additionally,the advanced high-throughput technologies and statistical methods employed can be learned and applied to disease prevention and treatment research.

Allergen-specific immunotherapy（AIT） remains the only therapeutic approach with the potential to modify the natural course of allergic rhinitis（AR）. Nevertheless, considerable inter-individual variability exists in patients'responses to AIT. To facilitate more reliable assessment of treatment efficacy, the China Rhinopathy Research Cooperation Group（CRRCG） convened young and middle-aged nasal experts in China to formulate the present consensus. The recommended subjective outcome measures for AIT comprise symptom scores, medication scores, combined symptom and medication scores, quality-of-life assessments, evaluation of disease control, and assessment of comorbidities. Objective indicators may supplement these measures. Currently available objective approaches include skin prick testing, nasal provocation testing, and allergen exposure chambers. However, these methods remain constrained by practical limitations and are not yet appropriate for routine implementation in clinical efficacy evaluation. In addition, several biomarkers, including sIgE and the sIgE/tIgE ratio, sIgG4, serum IgE-blocking activity, IgA, cytokines and chemokines, as well as immune cell surface molecules and their functional activity, have been shown to have associations with AIT outcomes. While these biomarkers may complement subjective assessments, they are subject to significant limitations. Consequently, large-scale multicenter trials and real-world evidence are required to strengthen the evidence base. The present consensus underscores the necessity of integrating patients'subjective experiences with objective testing throughout the treatment process, thereby providing a more comprehensive and accurate framework for efficacy evaluation. Looking forward, future investigations should prioritize the incorporation of multi-omics data and artificial intelligence methodologies, which hold promise for overcoming current limitations in assessment strategies and for advancing both the standardization and personalization of AIT.
Humans ; Allergens/immunology* ; China ; Consensus ; Desensitization, Immunologic ; Immunoglobulin E ; Quality of Life ; Rhinitis, Allergic/therapy* ; Treatment Outcome ; East Asian People

BACKGROUND: Knee osteoarthritis (OA) is still challenging to prevent or treat. Enhanced endoplasmic reticulum (ER) stress and increased pyroptosis in chondrocytes may be responsible for cartilage degeneration. This study aims to investigate the effect of ER stress on chondrocyte pyroptosis and the upstream regulatory mechanisms, which have rarely been reported. METHODS: The expression of the histone methyltransferase enhancer of zeste homolog 2 (EZH2), microRNA-142-3p (miR-142-3p), and high mobility group box 1 (HMGB1) and the levels of ER stress, pyroptosis, and metabolic markers in normal and OA chondrocytes were investigated by western blotting, quantitative polymerase chain reaction, immunohistochemistry, fluorescence in situ hybridization, fluorescein amidite-tyrosine-valine-alanine-aspartic acid-fluoromethyl ketone (FAM-YVAD-FMK)/Hoechst 33342/propidium iodide (PI) staining, lactate dehydrogenase (LDH) release assays, and cell viability assessments. The effects of EZH2, miR-142-3p, and HMGB1 on ER stress and pyroptosis and the hierarchical regulatory relationship between them were analyzed by chromatin immunoprecipitation, luciferase reporters, gain/loss-of-function assays, and rescue assays in interleukin (IL)-1β-induced OA chondrocytes. The mechanistic contribution of EZH2, miR-142-3p, and HMGB1 to chondrocyte ER stress and pyroptosis and therapeutic prospects were validated radiologically, histologically, and immunohistochemically in surgically induced OA rats. RESULTS: Increased EZH2 and HMGB1, decreased miR-142-3p, enhanced ER stress, and activated pyroptosis in chondrocytes were associated with OA occurrence and progression. EZH2 and HMGB1 exacerbated and miR-142-3p alleviated ER stress and pyroptosis in OA chondrocytes. EZH2 transcriptionally silenced miR-142-3p via H3K27 trimethylation, and miR-142-3p posttranscriptionally silenced HMGB1 by targeting the 3'-UTR of the HMGB1 gene. Moreover, ER stress mediated the effects of EZH2, miR-142-3p, and HMGB1 on chondrocyte pyroptosis. In vivo experiments mechanistically validated the hierarchical regulatory relationship between EZH2, miR-142-3p, and HMGB1 and their effects on chondrocyte ER stress and pyroptosis. CONCLUSIONS A novel EZH2/miR-142-3p/HMGB1 axis mediates chondrocyte pyroptosis and cartilage degeneration by regulating ER stress in OA, contributing novel mechanistic insights into OA pathogenesis and providing potential targets for future therapeutic research.
Enhancer of Zeste Homolog 2 Protein/genetics* ; Osteoarthritis, Knee/pathology* ; Chondrocytes/metabolism* ; Pyroptosis/physiology* ; HMGB1 Protein/genetics* ; MicroRNAs/metabolism* ; Endoplasmic Reticulum Stress/genetics* ; Humans ; Animals ; Rats ; Male ; Rats, Sprague-Dawley ; Middle Aged

Objective:To compare the application effects of the solution-focused nursing model (SFNM) and conventional care in the perioperative care for patients with pelvic fractures.Methods:A retrospective cohort study was conducted to analyze the clinical data of 62 patients with pelvic fractures admitted to the Third Affiliated Hospital of Southern Medical University between February 2023 and July 2023, including 41 males and 21 females, aged 26-63 years [(44.1±15.7)years]. All the patients underwent open or closed reduction and internal fixation. According to different perioperative nursing intervention, 31 patients were treated with conventional care (conventional care group) and 31 with SFNM intervention based on conventional care (SFNM group). A comparative analysis was conducted between the two groups regarding general self-efficacy scale (GSES) score, Barthel index (BI) score, self-rating anxiety scale (SAS) score, and self-rating depression scale (SDS) score preoperatively, at discharge, and at 6 months postoperatively. The excellent-to-good rate of Majeed pelvic function score and nursing satisfaction at the final follow-up and perioperative complication incidence were compared between the two group.Results:All the patients were followed up for 12-15 months [(13.5±0.9)months]. No significant differences were observed between the two groups in GSES, BI, SAS or SDS scores ( P>0.05). At discharge, the GSES and BI scores in the SFNM group were (29.0±3.8)points and (37.4±8.7)points, significantly higher than (20.9±3.0)points and (31.5±12.1)points in the conventional care group ( P<0.05); the SAS and SDS scores were (41.9±5.1)points and (40.6±4.9)points in the SFNM group, significantly lower than (53.7±9.1)points and (42.9±7.5)points in the conventional care group ( P<0.01). At 6 months postoperatively, the SFNM group achieved GSES and BI scores of (34.0±4.0)points and (40.3±9.0)points, significantly higher than (25.2±3.7)points and (35.7±10.5)points in the conventional care group ( P<0.05); the SAS and SDS scores were (45.8±5.0)points and (38.2±3.0)points in the SFNM group, significantly lower than (50.0±8.5)points and (40.7±6.5)points in the conventional care group ( P<0.01). At the final follow-up, the excellent-to-good rate of Majeed pelvic function score was 90% (28/31) in the SFNM group and 87% (27/31) in the conventional care group ( P>0.05). At the final follow-up, nursing satisfaction rate was 100% (31/31) in the SFNM group, significantly higher than 77% (24/31) in the conventional care group ( P<0.05). The perioperative complication rate was 6% (2/31) in the SFNM group, significantly lower than 38% (12/31) in the conventional care group ( P<0.05). Conclusion:Compared with conventional care, perioperative intervention with SFNM for patients with pelvic fractures can enhance self-efficacy and daily living self-care ability, reduce negative emotions such as anxiety and depression, improve nursing satisfaction, and lower the incidence of complications, making it worthy of clinical promotion.

Idiopathic pulmonary fibrosis (IPF) is a progressive disease lacking effective therapy. Metformin, an antidiabetic medication, has shown promising therapeutic properties in preclinical fibrosis models; however, its precise cellular targets and associated mechanisms in fibrosis resolution remain incompletely defined. Most research on metformin's effects has focused on mesenchymal and inflammatory responses with limited attention to epithelial cells. In this study, we utilized Sftpc lineage-traced and Fgfr2b conditional knockout mice, along with BMP2/PPARγ and AMPK inhibitors, to explore metformin's impact on alveolar epithelial cells in a bleomycin-induced pulmonary fibrosis model and cell culture. We found that metformin increased the proliferation and differentiation of alveolar type 2 (AT2) cells, particularly the recently identified injury-activated alveolar progenitors (IAAPs)-a subpopulation characterized by low SFTPC expression but enriched for PD-L1. Single-cell RNA sequencing revealed a reduction in apoptosis among mature AT2 cells. Interestingly, metformin's therapeutic effects were not significantly affected by BMP2 or PPARγ inhibition, which blocked the lipogenic differentiation of myofibroblasts. However, Fgfr2b deletion in Sftpc lineage cells significantly impaired metformin's ability to promote fibrosis resolution, a process linked to AMPK signaling. In conclusion, metformin alleviates fibrosis by directly activating AT2 cells, especially the IAAPs, through a mechanism that involves AMPK and FGFR2b signaling, but is largely independent of BMP2/PPARγ pathways.

The anti-inflammatory phytochemical investigation of the leaves of Illicium dunnianum (I. dunnianum) resulted in the isolation of five pairs of new lignans (1-5), and 7 known analogs (6-12). The separation of enantiomer mixtures 1-5 to 1a/1b-5a/5b was achieved using a chiral column with acetonitrile-water mixtures as eluents. The planar structures of 1-2 were previously undescribed, and the chiral separation and absolute configurations of 3-5 were reported for the first time. Their structures were determined through comprehensive spectroscopic data analysis [nuclear magnetic resonance (NMR), high-resolution electrospray ionization mass (HR-ESI-MS), infrared (IR), and ultraviolet (UV)] and quantum chemistry calculations (ECD). The new isolates were evaluated by measuring their inhibitory effect on NO in lipopolysaccharide (LPS)-stimulated BV-2 cells. Compounds 1a, 3a, 3b, and 5a demonstrated partial inhibition of NO production in a concentration-dependent manner. Western blot and real-time polymerase chain reaction (PCR) assays revealed that 1a down-regulated the messenger ribonucleic acid (mRNA) levels of tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), COX-2, and iNOS and the protein expressions of COX-2 and iNOS. This research provides guidance and evidence for the further development and utilization of I. dunnianum.
Lignans/isolation & purification* ; Plant Leaves/chemistry* ; Anti-Inflammatory Agents/isolation & purification* ; Mice ; Animals ; Molecular Structure ; Plant Extracts/pharmacology* ; Illicium/chemistry* ; Cyclooxygenase 2/immunology* ; Interleukin-6/immunology* ; Nitric Oxide/metabolism* ; Cell Line ; Tumor Necrosis Factor-alpha/immunology* ; Nitric Oxide Synthase Type II/immunology* ; Lipopolysaccharides

Objective:To retrospectively analyze the efficacy and feasibility of surgical management in patients with cervical dysphagia secondary to Diffuse idiopathic skeletal hyperostosis(DISH)of the cervical spine.Methods:A retrospective analysis was conducted on 6 patients who presented with dysphagia as the primary symptom, were diagnosed with cervical DISH, and underwent surgical treatment in the Department of Otorhinolaryngology Head and Neck Surgery of The Second Xiangya Hospital of Central South University from January 2018 to February 2024. There were 5 males and 1 female, aged from 65 to 78 years (70.2±4.7 years). The duration of dysphagia prior to admission was 13 to 18 months (14.7±2.2 months). All patients had the symptom of dysphagia, and at least one other clinical manifestation of cervical DISH (dyspnea, restricted neck mobility, sleep apnea, odynophagia). One patient had undergone tracheotomy due to laryngeal obstruction before surgery. Surgical intervention was performed after failure of conservative management in all patients. All patients underwent anterior cervical osteophyte resection via the Smith-Robinson approach without concomitant spinal fusion. In the patient with prior tracheotomy for airway obstruction, epiglottoplasty and right arytenoidectomy were performed simultaneously. The swallowing function was evaluated by water swallow test, FEES, M. D. Anderson Dysphagia Inventory. Clinical and imaging evaluations were conducted for follow-uppostoperatively. Preoperative and 30-day post operative data were statistically analyzed using paired samples t-test.Results:Cervical computed tomography revealed osteophyte involvement from C2 to T1 with a median of 4 vertebral segments affected. The most frequently involved vertebral segments were C4-C6 (all 6 patients were involved). The anteroposterior diameter of the most prominent osteophyte was 12.0 to 20.0 mm (16±3.1 mm). The time to resumption of a regular diet was 6 to 20 days(12.7±5.3 days), and the time to remove the nasogastric tube was 8 to 25 days(15.2±6.2 days). In the patient with prior tracheotomy, the tracheostomy tube was successfully decannulated 30 days after initial tube capping following conversion to a metal tube. All cervical DISH-related symptoms except for limited neck mobility improved postoperatively. Both water swallow test and the Rosenbek Penetration-Aspiration Scale showed significant improvement postoperatively. At 30 days postoperatively, MDADI scores significantly improved in all domains: l global (73.33±10.33), emotional (85.56±8.35), functional (83.33±5.89), and physical (82.08±6.60). No major perioperative complications occurred. and the length of hospital stay was 7 to 10 days (7.8±1.2 days). The follow-up time was 12 to 84 months (43.7±27.2 months). All patients maintained sustained symptom relief, with no evidence of osteophyte recurrence during follow-up.Conclusion:Cervical DISH is an under-recognized causes of dysphagia in elderly patients and warrants attention from otolaryngologists. For patients erefractory to conservative treatment, anterior resection of cervical osteophytes via the Smith-Robinson approach is a safe, minimally invasive procedure with favorable short-and long-term outcomes in improving swallowing function.

Objective:To investigate the effect of Zhuyu Tongluo Tang combined with manual release on isokinetic muscle strength and serum TGF-β1 and IGF-1 levels in patients with joint stiffness after ankle fracture surgery.Methods:A prospective study was conducted on 80 patients with ankle fractures who experienced joint stiffness during the recovery period after surgery at Nanchang Hongdu Traditional Chinese Medicine Hospital from March 2021 to March 2024.The patients were randomly divided into control group(n=40)and observation group(n=40)using a random number table method.Both groups of patients received routine intervention,followed by manual release therapy in control group;observation group received treatment in combination with Zhuyu Tongluo Tang on the basis of control group,with a treatment course of 4 weeks.Compared treatment outcomes,isokinetic muscle strength test indicators,American Orthopaedic of Foot and Ankle Society(AOFAS),ankle activity score(AAS),visual analog scale(VAS),traditional Chinese medicine syndrome score,and changes in dorsiflexion angle from two groups of patients before and after 4 weeks of treatment,and measured serum levels of TGF-β1 and insulin-like growth factor-1(IGF-1).Results:After treatment,effective rate of control group was 75.00%,while effective rate of observation group was 92.50%(P<0.05);PT,PT/BW and TW of observation group and control group were significantly increased,and PT,PT/BW and TW of observation group were significantly higher than those of control group(all P<0.05);AOFAS and AAS scores of observation group and control group were significantly increased,while VAS score was significantly decreased.AOFAS and AAS scores of observation group were significantly higher than those of control group,while VAS score was significantly lower than those of control group(both P<0.05);scores and total scores of various traditional Chinese medicine symptoms in observation group and control group were significantly reduced,and observation group was significantly lower than that in control group(both P<0.05);dorsiflexion angle of the foot in both observation group and control group were significantly increased,and the increase in observation group was greater than that in control group(both P<0.05);levels of TGF-β1 and IGF-1 in both obser-vation group and control group were significantly increased,and levels of TGF-β1 and IGF-1 in observation group were significantly higher than those in control group(both P<0.05).Conclusion:Combination of Zhuyu Tongluo Tang and manual release can improve the symptoms of joint stiffness and traditional Chinese medicine syndromes during the recovery period of ankle fractures,increase the functional score and isokinetic muscle strength index of the ankle joint,raise the levels of TGF-β1 and IGF-1,and improve the patient's dorsiflexion angle.This treatment regimen has good clinical efficacy.

Objective:To investigate the effect of Zhuyu Tongluo Tang combined with manual release on isokinetic muscle strength and serum TGF-β1 and IGF-1 levels in patients with joint stiffness after ankle fracture surgery.Methods:A prospective study was conducted on 80 patients with ankle fractures who experienced joint stiffness during the recovery period after surgery at Nanchang Hongdu Traditional Chinese Medicine Hospital from March 2021 to March 2024.The patients were randomly divided into control group(n=40)and observation group(n=40)using a random number table method.Both groups of patients received routine intervention,followed by manual release therapy in control group;observation group received treatment in combination with Zhuyu Tongluo Tang on the basis of control group,with a treatment course of 4 weeks.Compared treatment outcomes,isokinetic muscle strength test indicators,American Orthopaedic of Foot and Ankle Society(AOFAS),ankle activity score(AAS),visual analog scale(VAS),traditional Chinese medicine syndrome score,and changes in dorsiflexion angle from two groups of patients before and after 4 weeks of treatment,and measured serum levels of TGF-β1 and insulin-like growth factor-1(IGF-1).Results:After treatment,effective rate of control group was 75.00%,while effective rate of observation group was 92.50%(P<0.05);PT,PT/BW and TW of observation group and control group were significantly increased,and PT,PT/BW and TW of observation group were significantly higher than those of control group(all P<0.05);AOFAS and AAS scores of observation group and control group were significantly increased,while VAS score was significantly decreased.AOFAS and AAS scores of observation group were significantly higher than those of control group,while VAS score was significantly lower than those of control group(both P<0.05);scores and total scores of various traditional Chinese medicine symptoms in observation group and control group were significantly reduced,and observation group was significantly lower than that in control group(both P<0.05);dorsiflexion angle of the foot in both observation group and control group were significantly increased,and the increase in observation group was greater than that in control group(both P<0.05);levels of TGF-β1 and IGF-1 in both obser-vation group and control group were significantly increased,and levels of TGF-β1 and IGF-1 in observation group were significantly higher than those in control group(both P<0.05).Conclusion:Combination of Zhuyu Tongluo Tang and manual release can improve the symptoms of joint stiffness and traditional Chinese medicine syndromes during the recovery period of ankle fractures,increase the functional score and isokinetic muscle strength index of the ankle joint,raise the levels of TGF-β1 and IGF-1,and improve the patient's dorsiflexion angle.This treatment regimen has good clinical efficacy.